Mibrex

Package leaflet: Information for the patient

Mibrex, 10 mg, film-coated tablets
Rivaroxabanum
Please read the entire leaflet carefully before using the medicine, as it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any further questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, even if their symptoms of illness are the same.
• If you experience any adverse reactions, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents of the leaflet

1. What Mibrex is and what it is used for
2. Important information before taking Mibrex
3. How to take Mibrex
4. Possible side effects
5. How to store Mibrex
6. Contents of the pack and other information

1. What Mibrex is and what it is used for

Mibrex is an anticoagulant (a medicine that helps prevent the formation of blood clots). The active substance is rivaroxaban. Rivaroxaban belongs to a group of medicines called direct factor Xa inhibitors. It works by blocking a clotting factor in the blood called factor Xa, thereby reducing the ability of the blood to clot.

Mibrex is used to:

• Prevent venous thromboembolism (blood clots in the veins) in adults who have undergone surgery for hip or knee replacement.
• Prevent stroke and blood clots in adults with non-valvular atrial fibrillation (an irregular heart rhythm) who have at least one risk factor for stroke.
• Treat deep vein thrombosis (DVT - blood clots in the deep veins, usually in the legs) and pulmonary embolism (PE - blood clots in the lungs), and to prevent recurrence of DVT and PE in adults.
• Prevent atherothrombotic events (events caused by blood clots in the arteries) in adult patients with recent acute coronary syndrome (ACS) and elevated cardiac biomarkers, when administered together with acetylsalicylic acid (ASA) or ASA plus clopidogrel or prasugrel.
• Prevent stroke and systemic embolism in children and adolescents aged 6 to 17 years with non-valvular atrial fibrillation who have one or more risk factors for stroke.
• Treat venous thromboembolism and prevent recurrence of venous thromboembolism in children and adolescents aged 0 to 17 years.
• Prevent venous thromboembolism in children and adolescents aged 0 to 17 years undergoing certain surgical procedures associated with an increased risk of thrombosis.

2. Important information before using Mibrex

When not to use Mibrex:

• if the patient is allergic to rivaroxaban or any of the other ingredients of this medicine (listed in section 6),
• if the patient has excessive bleeding,
• if the patient has a disease or condition of an organ that leads to an increased risk of serious bleeding (e.g. stomach ulcer, trauma or bleeding in the brain, recent surgery on the brain or eyes),
• if the patient is taking other medicines that prevent blood clotting (e.g. warfarin, dabigatran, apixaban, or heparin), except when switching anticoagulant therapy or if heparin is administered to maintain catheter patency in a vein or artery,
• if the patient has a liver disease that leads to an increased risk of bleeding,
• if the patient is pregnant or breastfeeding.

Do not use Mibrex and inform your doctor if you suspect any of the above-mentioned conditions.
Warnings and precautions
Before starting to take Mibrex, discuss this with your doctor or pharmacist.
Exercise special caution when using Mibrex:

• if the patient has an increased risk of bleeding, such as in the following conditions:
  • moderate or severe kidney disease, as kidney function may affect the amount of medicine acting in the patient's body,
  • taking other medicines that prevent blood clotting (e.g. warfarin, dabigatran, apixaban, or heparin) when switching anticoagulant therapy or when heparin is administered to maintain catheter patency in a vein or artery (see section "Mibrex with other medicines"),
  • bleeding disorders,
  • very high blood pressure that does not decrease despite treatment with medication,
  • diseases of the stomach or intestines that may cause bleeding, e.g. inflammation of the intestines and stomach or inflammation of the oesophagus (throat and oesophagus), e.g. due to gastro-oesophageal reflux disease (backflow of stomach acid into the oesophagus), or tumours located in the stomach or intestines, or in the genital or urinary system,
  • blood vessel disease in the back of the eye (retinopathy),
  • lung disease with dilated airways filled with pus (bronchiectasis) or previous lung bleeding,
• in patients with heart valve prostheses,
• if the patient has a disorder called antiphospholipid syndrome (an immune system disorder causing an increased risk of blood clots), the patient should inform the doctor, who will decide whether treatment should be changed,
• if the patient has been diagnosed with abnormal blood pressure or if surgery or another treatment to remove a blood clot from the lungs is planned.

If the patient suspects any of the above-mentioned conditions, they should inform the doctor
before using Mibrex. The doctor will decide whether to use this medicine and whether the patient should be placed under particularly close observation.
If the patient needs to undergo surgery:

• strictly follow the doctor's instructions regarding the timing of taking Mibrex before and after surgery,
• if during surgery spinal catheterization or lumbar puncture is planned (e.g. for epidural or spinal anaesthesia or pain relief):
  • it is very important to take Mibrex exactly as directed by the doctor,
  • due to the need for special caution, immediately inform the doctor if numbness or weakness of the legs, or disturbances in bowel or bladder function occur after the anaesthesia ends.

Children and adolescents
Mibrex 10 mg tablets are not recommended for patients under 18 years of age. There is insufficient data on the use of the medicine in children and adolescents.
Mibrex with other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take, including those available without a prescription.
If the patient is taking
some medicines used to treat fungal infections (e.g. fluconazole, itraconazole, voriconazole, posaconazole), unless they are used only topically on the skin,
ketoconazole tablets (used in the treatment of Cushing's syndrome, in which the body produces too much cortisol),
some antibiotics used to treat bacterial infections (e.g. clarithromycin, erythromycin),
some antiviral medicines used in HIV infection or AIDS treatment (e.g. ritonavir),
other medicines used to reduce blood clotting (e.g. enoxaparin, clopidogrel, or vitamin K antagonists such as warfarin or acenocoumarol),
anti-inflammatory and pain-relieving medicines (e.g. naproxen or acetylsalicylic acid),
dronedarone, a medicine used to treat heart rhythm disorders,
some medicines used to treat depression (selective serotonin reuptake inhibitors (SSRI) or serotonin-noradrenaline reuptake inhibitors (SNRI)).
If the patient suspects any of the above-mentioned conditions, they should inform the doctor
before using Mibrex, as the effect of Mibrex may be enhanced.
The doctor will decide whether to use this medicine and whether the patient should be placed under particularly close observation.
If the doctor considers that the patient has an increased risk of developing stomach or intestinal ulcers, they may prescribe treatment to prevent ulcer formation.
If the patient is taking
some medicines used to treat epilepsy (phenytoin, carbamazepine, phenobarbital),
St. John's wort (Hypericum perforatum), a herbal medicine used for depression,
rifampicin, an antibiotic.
If the patient suspects any of the above-mentioned conditions, they should inform the doctor
before using Mibrex, as the effect of Mibrex may be reduced. The doctor will decide whether to use Mibrex and whether the patient should be placed under particularly close observation.
Pregnancy and breastfeeding
Do not use Mibrex if the patient is pregnant or breastfeeding. If there is a risk that the patient may become pregnant, an effective method of contraception should be used during treatment with Mibrex. If the patient becomes pregnant while taking this medicine, inform the doctor immediately, who will decide on further treatment.
Driving and operating machinery
Mibrex may cause dizziness (common side effects) or fainting (uncommon side effects) (see section 4 "Possible side effects"). Patients experiencing these side effects should not drive, ride a bicycle, or operate tools or machinery.
Mibrex contains lactose and sodium
If the patient has previously been diagnosed with intolerance to certain sugars, they should consult their doctor before taking this medicine.
The medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning the product is considered "sodium-free".

3. How to take Mibrex

This medicine should always be taken as directed by the physician. If in doubt, consult the doctor or pharmacist.
How many tablets to take

• To prevent the formation of blood clots in veins following hip or knee joint replacement surgery: The recommended dose is one 10 mg Mibrex tablet taken once daily.
• For the treatment of blood clots in the leg veins, blood clots in the blood vessels of the lungs, and to prevent recurrence of blood clots:

After at least 6 months of treatment for blood clots, the recommended dose is one 10 mg tablet once daily or one 20 mg tablet once daily. The doctor has prescribed Mibrex 10 mg once daily for the patient.
The tablet should be swallowed whole, preferably with water.
Mibrex can be taken with or without food.
If the patient has difficulty swallowing the whole tablet, discuss alternative methods of taking Mibrex with the doctor. The tablet may be crushed and mixed with water or apple puree immediately before administration. If necessary, the doctor may administer crushed Mibrex tablets via a gastric tube.
When to take Mibrex
Take one tablet every day until the doctor decides to stop treatment.
It is best to take the tablet at the same time each day, as this makes it easier to remember.
The duration of treatment will be determined by the doctor.
To prevent blood clots in veins after hip or knee joint replacement surgery:
The first tablet should be taken between 6 and 10 hours after surgery.
For patients undergoing major hip surgery, treatment usually lasts 5 weeks.
For patients undergoing major knee surgery, treatment usually lasts 2 weeks.
Taking more Mibrex than prescribed
If the patient has taken more than the prescribed dose of Mibrex, contact the doctor immediately. Overdosing on Mibrex increases the risk of bleeding.
Missed dose of Mibrex
If the patient forgets to take a dose, take the tablet as soon as remembered. Take the next tablet the following day, then continue taking the tablets as usual, once daily.
Do not take a double dose to make up for a missed dose.
Stopping Mibrex treatment
Do not stop taking Mibrex without first consulting the doctor, as Mibrex helps prevent serious illness.
If there are any further questions regarding the use of this medicine, consult the doctor.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everyone will experience them.
As with other medicines with a similar anticoagulant effect, Mibrex may cause bleeding, which potentially can be life-threatening. Excessive bleeding may lead to a sudden drop in blood pressure (shock). Signs of bleeding are not always obvious or visible.
You should immediately contact your doctor if any of the following adverse reactions occur:

• Signs of bleeding:
  • bleeding into the brain or inside the skull (symptoms may include headache, one-sided paralysis, vomiting, seizures, decreased level of consciousness and neck stiffness. This is a serious medical emergency. Seek immediate medical help!),
• prolonged or excessive bleeding,
• unusual weakness, fatigue, paleness, dizziness, headache, unexplained swelling, shortness of breath, chest pain or angina. Your doctor may decide that close monitoring of the patient or a change in treatment is necessary.
  • Signs of severe skin reactions:
• extensive, acute skin rash, blistering or mucosal lesions (e.g. in the mouth or eyes) (Stevens-Johnson syndrome, toxic epidermal necrolysis).
• drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), characterized by rash, fever, internal organ inflammation, hematological disorders and systemic involvement. The frequency of these adverse reactions is very rare (occurring in up to 1 in 10,000 people).
  • Signs of serious allergic reactions
• swelling of the face, lips, oral cavity, tongue or throat; urticaria and breathing difficulties; sudden drop in blood pressure. The frequency of severe allergic reactions is very rare (anaphylactic reactions, including anaphylactic shock, may occur in up to 1 in 10,000 people) and uncommon (angioedema and allergic edema may occur in 1 in 100 people).

General list of possible adverse reactions:
Common (may occur in 1 in 10 patients)

• decreased number of red blood cells, which may cause paleness of the skin and lead to weakness or shortness of breath,
• gastrointestinal bleeding or intestinal bleeding, bleeding from the urinary or genital tract (including blood in urine and severe menstrual bleeding), nosebleeds, gum bleeding,
• ocular bleeding (including bleeding from the conjunctiva),
• bleeding into tissues or body cavities (hematoma, bruising),
• presence of blood in sputum (hemoptysis) during coughing,
• skin bleeding or subcutaneous bleeding,
• postoperative bleeding,
• oozing of blood or fluid from a surgical wound,
• limb swelling,
• limb pain,
• kidney function disorders (may be observed in tests performed by a doctor),
• fever,
• stomach pain, indigestion, nausea or vomiting, constipation, diarrhea,
• low blood pressure (symptoms may include dizziness or fainting upon standing),
• general decrease in strength and energy (weakness, fatigue), headache, dizziness,
• rash, itching of the skin,
• increased activity of certain liver enzymes, which may be evident in blood test results.

Uncommon (may occur in 1 in 100 patients)

• intracranial bleeding or bleeding within the skull (see signs of bleeding above),
• joint bleeding causing pain and swelling,
• thrombocytopenia (low platelet count, blood cells involved in blood clotting),
• allergic reactions, including allergic skin reactions,
• liver function disorders (may be observed in tests performed by a doctor),
• blood tests may show increased levels of bilirubin, increased activity of certain pancreatic or liver enzymes, or increased platelet count,
• fainting,
• malaise,
• rapid heartbeat,
• dryness of the mouth,
• urticaria.

Rare (may occur in 1 in 1,000 patients)

• muscle bleeding,
• cholestasis (bile stasis), hepatitis including liver cell damage,
• yellowing of the skin and eyes (jaundice),
• local swelling,
• blood collection (hematoma) in the groin as a complication of cardiac catheterization procedure, when the catheter is inserted into an artery in the leg (pseudoaneurysm).

Very rare (may occur in 1 in 10,000 patients)

• accumulation of eosinophils, a type of white granulocytic blood cells, causing lung inflammation (eosinophilic pneumonia).

Frequency not known (frequency cannot be determined from available data)

• kidney failure following severe bleeding,
• kidney bleeding, sometimes with presence of blood in urine, leading to impaired kidney function (drug-induced anticoagulant-related nephropathy),
• increased pressure within the muscles of arms and legs following bleeding, which may lead to pain, swelling, altered sensation, numbness or paralysis (compartment syndrome following bleeding).

Reporting of adverse reactions
If any adverse symptoms occur, including any adverse symptoms not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: + 48 22 49 21 301
Fax: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Mibrex

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister. The expiry date refers to the last day of the stated month.
The labelling on the packaging following the abbreviation EXP indicates the expiry date, and following the abbreviation Lot/LOT indicates the batch number.
No special storage conditions are required for this medicine.
Crushed tablets
Crushed tablets are stable in water or apple puree for up to 4 hours.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Mibrex contains

• The active substance is rivaroxaban. Each coated tablet contains 10 mg of rivaroxaban.
• Other ingredients are: tablet core: sodium lauryl sulfate, monohydrate lactose, microcrystalline cellulose, sodium croscarmellose, hypromellose, magnesium stearate.
  tablet coating (Opadry II Pink 33G34170): hypromellose, titanium dioxide (E 171), monohydrate lactose, macrogol 3350, triacetin, yellow iron oxide (E 172), black iron oxide (E 172), red iron oxide (E 172).

What Mibrex looks like and contents of the pack
Mibrex 10 mg are pink, round, biconvex coated tablets, with the number "10" embossed on one side.
The tablets are contained in transparent blisters made of Aluminium /PVC/PVDC foil, packed in cardboard boxes containing 5, 10, 14, 28, 30, 56, 60 or 98 coated tablets, or in single-dose perforated blisters made of Aluminium /PVC/PVDC foil, packed in cardboard boxes containing 10 x 1 tablet or 100 x 1 tablet, or in multipacks containing 10 boxes, each with 10 x 1 coated tablet.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Zakłady Farmaceutyczne POLPHARMA S.A.
ul. Pelplińska 19
83-200 Starogard Gdański
tel. + 48 22 364 61 01